Behind the scenes: epigenetic mechanisms rule the roost in pubertal timing.
Behind the scenes: epigenetic mechanisms rule the roost in pubertal timing.
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DOI：
10.1016/s2213-8587(23)00167-5
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发表时间：
2023-06
期刊：
影响因子：
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通讯作者：
Ravikumar Balasubramanian
中科院分区：
文献类型：
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作者：
Ravikumar Balasubramanian
在人类中，在童年时期经历了一段神秘的静止期后，下丘脑的促性腺激素释放激素（GnRH）脉冲式分泌的重新激活标志着青春期的开始。[1]控制这种动态发育转变的精确分子触发因素仍然难以捉摸。GnRH脉冲性分泌的早期再激活在临床上表现为中枢性性早熟。在过去的二十年里，中枢性性早熟的遗传学研究已经开始揭示重新激活人类GnRH脉冲分泌的关键分子决定因素。2然而，中枢性早熟的完整遗传结构和导致中枢性早熟的基因的完整集合仍然不清楚，特别是在散发性中枢性早熟表现中。因此，中枢性性早熟的遗传学研究提供了一个独特的机会，以解开控制青春期开始的分子驱动因素。青春期时间的改变，包括青春期的早期和晚期，通常被认为是具有不同遗传原因的多系统综合征性发育障碍患者的组成表型。Rett综合征是一种严重的进行性神经发育障碍，其特征是在典型发育期后语言和运动技能迅速退化。3重复的刻板运动（绞手）取代了有目的的手部运动，除了这些运动症状外，患者还具有复杂的表型，伴有多种合并症。在
In humans, following a mysterious quiescence during childhood, the reactivation of pulsatile secretion of gonadotropin-releasing hormone (GnRH) from the hypothalamus marks the onset of puberty. 1 The precise molecular triggers that govern this dynamic developmental transition remain elusive. Early reactiva tion of pulsatile GnRH secretion presents clinically as central precocious puberty. Over the past two decades, genetic studies in central precocious puberty have begun to shed light into the crucial molecular determinants that reactivate pulsatile GnRH secretion in humans. 2 However, the full genetic architecture of central precocious puberty and full ensemble of genes contributing to the cause of central precocious puberty remain unclear, especially in sporadic central precocious puberty presentations. Hence, genetic investigation of central precocious puberty provides a unique opportunity to unravel the molecular drivers governing the initiation of puberty. Altered pubertal timing, both early and late puberty, is often recognised as a constituent phenotype in patients presenting with multisystem syndromic developmental disorders with varied genetic causes. 2 Rett syndrome is a severe progressive neurodevelopmental disorder, characterised by rapid regression in language and motor skills following a period of typical development. 3 Repetitive stereotypical movement (hand-wringing) replaces purposeful hand movements and in addition to these motor symptoms, patients have a complex phenotype with multiple comorbidities. In